The Impact of Combined Chemotherapy and Intra-Tumoural Injection of Phosphorus-32 Microparticles on Vascularity in Locally Advanced Pancreatic Carcinoma.

Simple Summary: Despite the advances in medicine, the 5-year survival rate for pancreatic ductal adenocarcinoma (PDAC) is still dismal and has not improved. New treatment options are required. Some data have been promising for endoscopic ultrasound-guided phosphorus-32 (³²P) microparticle implantation. Given the role of poor vascularisation in the poor response of pancreatic cancer to standard therapy, such as chemotherapy, we hypothesised that EUS-guided ³²P microparticle implantation improves chemotherapy delivery to and effects on the primary tumour. No treatment option has been shown to consistently improve tumour vascularity in PDAC, but a treatment that is able to improve vascularity may work synergistically with chemotherapy to improve outcomes in PDAC. Background: Poor intra-tumoural vascularity contributes to a lack of response to chemotherapy in pancreatic cancers. Preliminary data suggest that the addition of endoscopic ultrasound (EUS)-guided intra-tumoural injection of phosphorus-32 (³²P) microparticles to standard chemotherapy is potentially beneficial in locally advanced pancreatic cancer (LAPC). We aimed to assess changes in pancreatic tumour vascularity following ³²P implantation, using contrast-enhanced EUS (CE-EUS). Methods: This was a prospective single-centre trial from January 2022 to 2024 of patients with unresectable, non-metastatic LAPC undergoing standard FOLFIRINOX chemotherapy and ³²P implantation. We performed CE-EUS pre-implantation after two chemotherapy cycles and 4 and 12 weeks after implantation. Time–intensity curves were analysed for 90 s after IV contrast bolus to ascertain peak intensity and intensity gain. Results: A total of 20 patients underwent ³²P implantation, with 15 completing 12-week follow-up. The technical success of ³²P implantation was 100%. The median primary tumour size reduced from 32 mm (IQR 27.5–38.75) pre-implantation to 24 mm (IQR 16–26) 12 weeks post-implantation (p < 0.001). Five patients (25%) had tumour downstaging, and four underwent resections. The baseline (pre-implantation, post-chemotherapy) median intensity gain of contrast enhancement within the tumour was 32.15 (IQR 18.08–54.35). This increased to 46.85 (IQR 35.05–76.6; p = 0.007) and 66.3 (IQR 54.7–76.3; p = 0.001) at 4 weeks and 12 weeks post-implantation, respectively. Over a median follow-up of 11.2 months (IQR 7.8–12.8), 15/20 (75%) of patients remained alive, with 3/20 (15%) demonstrating local disease progression. Overall survival was not significantly different between patients with or without an increased intensity of 10 a.u. or more at 12 weeks post-implantation. Conclusion: This is the first clinical study to demonstrate treatment-induced increased vascularity within pancreatic primary tumours, which followed ³²P implantation and FOLFIRINOX chemotherapy. Larger comparative trials are warranted. [ABSTRACT FROM AUTHOR]